An in vitro study of ectopic discharge generation and adrenergic sensitivity in the intact, nerve-injured rat dorsal root ganglion

Pain. 1997 Aug;72(1-2):51-7. doi: 10.1016/s0304-3959(97)00013-4.

Abstract

A chronic, loose constriction of the sciatic nerve in rat produces behavioral signs of spontaneous pain and cutaneous hyperalgesia (Bennett and Xie, Pain, 33 (1988) 87-107) as well as an abnormal spontaneous activity and adrenergic sensitivity of certain dorsal root ganglion (DRG) cells with axons in the injured nerve (Kajander et al., Neurosci. Lett., 138 (1992) 225-228; Xie et al., J. Neurophysiol., 73 (1995)1811-1820). The present study investigated whether the spontaneous activity and adrenergic sensitivity were intrinsic properties of injured DRG cells and manifested in vitro, i.e., not dependent on intact blood circulation and an intact, functioning sympathetic nervous system. Two weeks after a loose constriction of the sciatic nerve, the L4 or L5 DRG with its ligated nerve and dorsal root attached was removed from the rat and placed in a chamber. Extracellular recordings were made from teased dorsal root fibers. Spontaneous activity (>0.05 imp/s in 3 min) originating within or close to the DRG was often found in C-, Adelta- and Abeta-fibers from nerve-injured rats, but was rare in fibers with peripheral axons from uninjured nerve. The incidence of various patterns of spontaneous discharge was similar to that previously recorded in vivo. Nineteen of 30 C-fibers, four of five Adelta- and three of seven Abeta-fibers from injured nerve responded to different doses of norepinephrine (NE) applied topically to the DRG. Five of seven C- and one of two Abeta -fibers from injured nerve responded to clonidine, a more selective alpha2 adrenergic agonist. The thresholds ranged from 500 to 10 microM, the lowest dose delivered. None of the fibers from uninjured nerve responded to NE or clonidine (500 microM). Since the experiments were carried out in vitro in the intact DRG, the existence of spontaneous activity in DRG cells in nerve-injured rats was independent of any blood borne chemicals, such as norepinephrine. We hypothesize that abnormal activity and adrenergic sensitivity in injured DRG neurons are due to an intrinsic alteration of the cell body membrane.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials / physiology
  • Adrenergic alpha-Agonists / pharmacology*
  • Animals
  • Clonidine / pharmacology
  • Electric Stimulation
  • Ganglia, Spinal / injuries*
  • Ganglia, Spinal / pathology
  • In Vitro Techniques
  • Male
  • Nerve Fibers / drug effects
  • Neurons / drug effects
  • Norepinephrine / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Sciatic Nerve / injuries*

Substances

  • Adrenergic alpha-Agonists
  • Clonidine
  • Norepinephrine